Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Alfred Health, Commercial Road, Melbourne, Victoria, Australia.
BMC Musculoskelet Disord. 2021 Sep 27;22(1):826. doi: 10.1186/s12891-021-04690-y.
Knee osteoarthritis is a major cause of pain and disability. Pain control is poor, with most patients remaining in moderate to severe pain. This may be because central causes of pain, a common contributor to knee pain, are not affected by current treatment strategies. Antidepressants, such as amitriptyline, have been used to treat chronic pain in other conditions. The aim of this randomised, double blind, controlled trial, is to determine whether low dose amitriptyline reduces pain in people with painful knee osteoarthritis over 3 months compared to benztropine, an active placebo.
METHODS/DESIGN: One hundred and sixty people with painful radiographic knee osteoarthritis will be recruited via clinicians, local and social media advertising. Participants will be randomly allocated in a 1:1 ratio to receive either low dose amitriptyline (25 mg) or active placebo (benztropine mesylate, 1 mg) for 3 months. The primary outcome is change from baseline in knee pain (WOMAC pain subscale) at 12 weeks. Secondary outcomes include change in function (total WOMAC) and the proportion of individuals achieving a substantial response (≥ 50% reduction in pain intensity, measured by Visual Analog Scale, VAS, from no pain to worst pain imaginable, 0-100 mm) and moderate response (≥ 30% reduction in pain intensity, measured by VAS) at 12 weeks. Intention to treat analyses will be performed. Subgroup analyses will be done.
This study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA. This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record.
Australian New Zealand Clinical Trials Registry prior to recruitment commencing ( ACTRN12615000301561 , March 31, 2015, amended 14 December 2018, February 2021). Additional amendment requested 18 July 2021.
膝骨关节炎是疼痛和残疾的主要原因。疼痛控制效果不佳，大多数患者仍处于中度至重度疼痛。这可能是因为疼痛的中枢原因，即膝痛的常见病因，不受当前治疗策略的影响。三环类抗抑郁药，如阿米替林，已被用于治疗其他疾病的慢性疼痛。本随机、双盲、对照试验的目的是确定低剂量阿米替林是否能在 3 个月内减轻膝关节疼痛患者的疼痛，与阳性对照苯扎托品相比。
方法/设计：通过临床医生、当地和社交媒体广告招募 160 名患有放射性膝关节骨关节炎疼痛的患者。参与者将以 1:1 的比例随机分配接受低剂量阿米替林（25mg）或阳性对照（苯扎托品甲硫酸盐，1mg）治疗 3 个月。主要结局是 12 周时膝关节疼痛（WOMAC 疼痛量表）的基线变化。次要结局包括功能变化（WOMAC 总分）和达到显著缓解（疼痛强度降低≥50%，用视觉模拟量表（VAS）从无痛到可想象的最痛，0-100mm）和中度缓解（疼痛强度降低≥30%，用 VAS）的个体比例在 12 周时。将进行意向治疗分析。将进行亚组分析。
本研究将提供高水平的证据，证明与苯扎托品相比，低剂量阿米替林在减轻膝骨关节炎疼痛和改善功能方面的有效性。这项试验有可能为膝骨关节炎的疼痛管理提供一种有效的新治疗方法，有可能迅速转化为临床实践，因为它重新利用了一种熟悉的老药物，且具有良好的安全性记录。
在招募开始前（澳大利亚新西兰临床试验注册中心，ACTRN12615000301561，2015 年 3 月 31 日，2018 年 12 月 14 日修订，2021 年 2 月修订）。2021 年 7 月 18 日请求增加额外的修正案。
